This project is directed, in the broadest sense, to the understanding of the chemical architecture of the brain and particularly the macromolecular complexes of the myelin sheath. During the proposed project period the problem to be studied concerns the chemistry of proteolipids from brain subcortical white matter. Proteolipids are defined as lipoproteins which are soluble in chloroform-methanol and insoluble in water. The proteolipid apoprotein can be obtained free of complex lipids in a form still soluble in chloroform-methanol but which can be converted to a water soluble form. The program is specifically directed toward the determination of the complete amino acid sequence of the "classical" white matter proteolipid of Folch and Lees with the purpose of characterizing the nature of the sequences which give rise to the unusual solubility of the protein. Sufficient information is now available on the white matter proteolipid to make such a study feasible. The program will require the preparation of chemically modified proteolipids, the controlled enzymatic and chemical cleavage of the protein and the separation and purification of sufficient amounts of peptides for sequencing. In the course of these studies, information on the chemical properties and possible subunit structure of the proteolipid will be obtained. In addition, it should be possible to locate the position of the covalently bound fatty acid residues in the apoprotein. Comparable sequence studies will be carried out on proteolipids from other animal species and other brain regions. The procedures for sequencing will also provide peptides and chemically modified proteins to be used for studies of the encephalitogenic and antigenic properties of the proteolipid apoprotein. The observation that proteolipids can be cleaved in vitro by proteolytic enzymes makes these investigations applicable to an understanding of multiple sclerosis and could potentially provide either a new animal model or a diagnostic test for susceptibility to MS.